Ketamine's Effect Changes the Cortical Electrophysiological Activity Related to Semantic Affective Dimension of Pain

Ketamine's Effect Changes the Cortical Electrophysiological Activity Related to Semantic Affective Dimension of Pain: a Placebo-controlled Study in Healthy Male Subjects

This is a clinical trial that intend to determine the effects of S-ketamine on event-related potentials associated with semantic affective pain-processing

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Acute Pain; Chronic Pain, Widespread
• Intervention / Treatment: Drug: Ketamine; Drug: Placebo

Detailed Description

Ketamine is a unique anesthetic with neural effects that are distinct from more commonly-used γ-aminobutyric acid agonists. Evidence suggest that analgesic effect of ketamine is primarily related to the affective than the sensorial aspects of pain interpretation. The investigators investigated whether ketamine, a noncompetitive NMDA antagonist, would modify the perceived emotional valence of pain-related words when compared to non-pain-related ones in healthy volunteers. Using a single session double-blind parallel placebo-controlled design, 24 healthy volunteers were randomized to receive intravenous S-ketamine (n=12) or placebo (n=12). During infusion (plasmatic target of 60 ng/ml), the effects of ketamine were recorded using EEG and oddball behavioral data was monitored. Evoked potentials (N200 and P300 components) were recorded during performance of a semantic written word oddball task containing pain-related (targets) and non-pain-related words (standards). Expected results: The findings of this study can help in the understanding of neurophysiologic mechanisms involved in ketamine's effects both in psychiatric diseases as in the treatment of postoperative acute and chronic pain.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• male healthy subjects with higher education level

Exclusion Criteria:

• do not understand Portuguese language
• obese patients (BMI > 27 kg/m2)
• use of NSAID, steroids, analgesics, anticonvulsant drugs, as well as alpha and beta-blockers
• score ≥ 13 on Beck II Questionnaire
• sleep deprivation in the night before evaluation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group S-Ketamine; S-Ketamine will be diluted in normal saline and administrated in a target controlled infusion using an infusion pump to obtain a plasma target of 60 ng/ml according to Domino's model. Infusion will start during the interval between the 3rd and 4th blocks of the task.	Drug: Ketamine; S-ketamine will be administered in precalculated infusion rates to obtain a plasmatic level of 60 ng/ml
Placebo Comparator: Group Placebo; A previously prepared identical solution containing only normal saline will be infused at the same infusion rates of group ketamine.	Drug: Placebo; Administered in an identical way than ketamine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC of the grand averaged mean differences between ERPs elicited by target and non-target words	EEG will be recorded during all task time. The main outcome will be the area under de curve (AUC) of the grand averaged mean differences between event-related potencials (ERPs) elicited by target and non-target words at 100-200, 300-500 and 800-900 ms after stimulus presentation for parietal electrophysiological signal (Pz). The ERPs represent the averaged voltage of several trials.	up to 60 min

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Word ratings related to the semantic valence	After viewing each word, volunteers were asked to classify them according to the semantic valence in the following categories: "positive," "negative" or "neutral."	up to 60 min
Response times (behavioural oddball data)	Response times to word classification in oddball task	up to 60 min

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective euphoria rating	Euphoria will be rated using an analogue visual scale ranging of 0 to 10.	up to 60 min
Subjective sedation rating	Sedation will be rated using an analogue visual scale ranging of 0 (completely awake) to 100 (sleeping).	up to 60 min

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Investigators: Principal Investigator: Wolnei Caumo, MD, PhD, Hospital de Clínicas de Porto Alegre

Publications and helpful links

General Publications

• Schwertner A, Zortea M, Torres FV, Ramalho L, Alves CFDS, Lannig G, Torres ILS, Fregni F, Gauer G, Caumo W. S-Ketamine's Effect Changes the Cortical Electrophysiological Activity Related to Semantic Affective Dimension of Pain: A Placebo- Controlled Study in Healthy Male Individuals. Front Neurosci. 2019 Sep 13;13:959. doi: 10.3389/fnins.2019.00959. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2017
• Primary Completion (Actual): November 30, 2017
• Study Completion (Actual): November 30, 2017

Study Registration Dates

• First Submitted: April 12, 2019
• First Submitted That Met QC Criteria: April 15, 2019
• First Posted (Actual): April 16, 2019

Study Record Updates

• Last Update Posted (Actual): April 16, 2019
• Last Update Submitted That Met QC Criteria: April 15, 2019
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Ketamine; ERP; Oddball
• Additional Relevant MeSH Terms: Mental Disorders; Pain; Neurologic Manifestations; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Chronic Pain; Acute Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 15-0019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No